DIRECTLY GUIDING immune cells to the centre of inflammation zones may soon become reality, as suggested by results found at the Cells-in-Motion Cluster of Excellence at the University of Münster, Münster, Germany. The research team aimed to control the disease-driving side effects of phagocyte migration through genetically modifying immune cells, and this new technique holds hope as a new therapeutic strategy that minimises additional, unnecessary damage to tissues while also minimising the use of laboratory animals.
Usually, investigating phagocyte migration paths towards inflammatory sites requires a large number of specifically bred, genetically modified mice that display inflammatory diseases. Using immortalised myeloid precursor cells, known as ER-Hoxb8 cells, the researchers at the University of Münster have overcome this issue. ER-Hoxb8 cells can multiply almost without limit within test tubes and, with the right conditions, can differentiate into many immune cell types, enabling immune cells to be obtained without the need for large numbers of mice. The researchers took advantage of this technique to produce genetically modified immune cells that lacked VLA4, a protein essential for migration, mimicking conditions in innate immune deficiencies. The cells were then fluorescently labelled and injected into mice displaying an inflammatory skin condition, alongside fluorescently labelled healthy immune cells. Using fluorescence reflectance imaging, the researchers were able to visualise and compare the ways the different immune cells moved around the body.
The scientists then tested this technique in mice that had experienced a heart attack using single photon emission tomography to create digital cross-sections of the heart, allowing easy visualisation of the deep tissues. In doing so, the researchers established how the different immune cells move and react in inflammatory conditions. They hold hope for this new technique to be used in other inflammatory conditions, such as infections and rheumatological and arthritic disorders. Through understanding the inflammatory pathways and behaviour of immune cells within each condition, it will be possible to create individual treatment methods by modifying and targeting immune cells directly to the centre of inflammation sites. “As a result of our new method, we can now, for the first time, genetically modify different types of immune cells at will and deactivate important inflammation mechanisms,” concluded lead author Dr Sandra Gran, University of Münster.